Abstract
Extracellular ATP acts through endothelial cell (EC) purinoceptors to produce vasodilation of cerebral arteries (CA). IKCa channels have been established in this mechanism; however, the role of SKCa channels is not clear. We hypothesize that sustained ATP‐mediated hyperpolarization and vasodilation requires Ca2+ influx via EC TRPC3 channels to produce activation of SKCa channels.MethodsVascular diameter was measured following luminal delivery of ATP in mouse pressurized superior cerebellar arteries (SCA). Changes in EC Ca2+ were measured by biosensor in SCA isolated from Cx40BAC‐GCaMP2 transgenic mice. Membrane currents and voltage were measured in freshly isolated EC from CA of WT and TRPC3 knock out (KO) mice using perforated patch whole cell recording in voltage or current clamp mode.ResultsApplication of a selective TRPC3 blocker (Pyr3) significantly attenuated the duration of endothelial Ca2+ increase and vasodilation to ATP in pressurized SCA and abbreviated ATP‐mediated hyperpolarization in freshly isolated ECs. Responses were replicated with arteries and EC isolated from TRPC3 KO mice. Selective SKCa channel inhibition (UCL1684) mirrored the abbreviated time course of EC hyperpolarization, suggesting a common pathway.ConclusionWe propose that Ca2+ influx via TRPC3 promotes SKCa activation to produce the sustained component of cerebral vasorelaxation to ATP. Supported by R01HL088435 to SPM
Published Version
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